Abstract
Background
KRAS mutations may predict poor response to radiotherapy. Downstream events from KRAS, such as activation of BRAF, AKT and ERK, may also confer prognostic information but have not been tested in rectal cancer (RC). Our objective was to explore the relationships of KRAS and BRAF mutation status with p-AKT and p-ERK and outcomes in RC.
Methods
Pre-radiotherapy RC tumor biopsies were evaluated. KRAS and BRAF mutations were assessed by pyrosequencing; p-AKT and p-ERK expression by immunohistochemistry.
Results
Of 70 patients, mean age was 58; 36% stage II, 56% stage III, and 9% stage IV. Responses to neoadjuvant chemoradiotherapy: 64% limited, 19% major, and 17% pathologic complete response. 64% were KRAS WT, 95% were BRAF WT. High p-ERK levels were associated with improved OS but not for p-AKT. High levels of p-AKT and p-ERK expression were associated with better responses. KRAS WT correlated with lower p-AKT expression but not p-ERK expression. No differences in OS, residual disease, or tumor downstaging were detected by KRAS status.
Conclusions
KRAS mutation was not associated with lesser response to chemoradiotherapy or worse OS. High p-ERK expression was associated with better OS and response. Higher p-AKT expression was correlated with better response but not OS.

Davies, Janine MAffiliation: Division of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill

Trembath, DimitriAffiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill

Funkhouser, William KAffiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill

Calvo, Benjamin FAffiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
Division of Surgical Oncology, Department of Sugery, School of Medicine, University of North Carolina at Chapel Hill

Weck, Karen EAffiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill

Tepper, Joel EAffiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
Department of Radiation Oncology, University of North Carolina at Chapel Hill

O'Neil, Bert HAffiliation: Division of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill

Title

Phospho-ERK and AKT status, but not KRAS mutation status, are associated with outcomes in rectal cancer treated with chemoradiotherapy